Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions.

BACKGROUND: C-C motif chemokine ligand 2, a gene that codes for a protein involved in inflammation. Certain SNPs in the CCL2 gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in CCL2 may influence the immune response to Mycobacterium leprae infection. OBJECTIVE: To investigate the association of the C-C motif chemokine ligand-2 single nucleotide polymorphisms with leprosy. METHODS: CCL2 single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for CCL2 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for CCL2 -2134 T>G, 325 leprosy and 288 controls for CCL2 -1549 A>T SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-ß were estimated in sera samples and correlated with CCL2 genotypes. RESULTS: The frequency of the GCT (-2518 A>G, -362 G>C, -2134 T>G) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-2518A>G, p = 0.53), (-362 G>C, p = 0.01), (-2134 T>G, p = 0.10)}. G allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). GG genotype (p = 0.008) and G allele at -2518 (p = 0.030) of the CCL 2 gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -2518 AA and AG genotypes (p = 0.0001). CONCLUSIONS: G allele and GG genotype at the CCL2 -2518 site are associated with a risk of ENL reactions.

The Burden and Correlates of Waterpipe (Hookah) Smoking among Adolescents and Youth: A Systematic Review.

BACKGROUND: This systematic review evaluated the available medical literature on the prevalence and trends of waterpipe tobacco smoking among adolescents and youth in jurisdictionally representative populations. METHODS: PubMed, Embase, and Scopus were searched for relevant studies from inception until 31 December 2022 that reported the burden of waterpipe smoking among adolescents and youth (10-24 years of age). We extracted qualitative data on the demographic characteristics, burden, and correlates of waterpipe smoking (PROSPERO ID: CRD42022310982). RESULTS: A total of 2,197 articles were screened and 62 were included in the analysis. The majority (29) of the studies was from the United States of America and there were no studies from the south-east Asian region. The prevalence of ever waterpipe smoking among the 10-24 years age group was noted to be 18.16% (95% CI, 18.03-18.29). The prevalence of current (30-day) waterpipe smoking was 6.43% (95% CI, 6.34-6.50). The age of initiation of waterpipe smoking was variable. The prevalence of waterpipe smoking was higher among males, among those who belong to the high- and middle-income groups, and among university students. The common risk factors of waterpipe smoking included cigarette smoking, alcohol, and substance use. Waterpipe smoking resulted in increased susceptibility to the use of conventional forms of tobacco (e.g. smoking) among those who were never smokers. CONCLUSION: Waterpipe smoking usage was significantly high among adolescents and young adults. Developing regulatory guidelines for water-pipe smoking, surveillance of its use, intervention, and specific policy frameworks may be considered a public health priority.

Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial.

Background: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. Patients and methods: European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Results: Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no: NCT04238416 (clinicaltrials.gov).

Smart Crop Cultivation System Using Automated Agriculture Monitoring Environment in the Context of Bangladesh Agriculture.

The Internet of Things (IoT) is a transformative technology that is reshaping industries and daily life, leading us towards a connected future that is full of possibilities and innovations. In this paper, we present a robust framework for the application of Internet of Things (IoT) technology in the agricultural sector in Bangladesh. The framework encompasses the integration of IoT, data mining techniques, and cloud monitoring systems to enhance productivity, improve water management, and provide real-time crop forecasting. We conducted rigorous experimentation on the framework. We achieve an accuracy of 87.38% for the proposed model in predicting data harvest. Our findings highlight the effectiveness and transparency of the framework, underscoring the significant potential of the IoT in transforming agriculture and empowering farmers with data-driven decision-making capabilities. The proposed framework might be very impactful in real-life agriculture, especially for monsoon agriculture-based countries like Bangladesh.

Mortality Associated with Ambient PM2.5 Exposure in India: Results from the Million Death Study.

BACKGROUND: Studies on the extent to which long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5) contributes to adult mortality in India are few, despite over 99% of Indians being exposed to levels that the World Health Organization (WHO) considers unsafe. OBJECTIVE: We conducted a retrospective cohort study within the Million Death Study (MDS) to provide the first-ever quantification of national mortality from exposure to PM2.5 in India from 1999 to 2014. METHODS: We calculated relative risks (RRs) by linking a total of ten 3-y intervals of satellite-based estimated PM2.5 exposure to deaths 3 to 5 y later in over 7,400 small villages or urban blocks covering a total population of 6.8 million. We applied using a model-based geostatistical model, adjusted for individual age, sex, and year of death; smoking prevalence, rural/urban residency, area-level female illiteracy, languages, and spatial clustering and unit-level variation. RESULTS: PM2.5 exposure levels increased from 1999 to 2014, particularly in central and eastern India. Among 212,573 deaths at ages 15-69 y, after spatial adjustment, we found a significant RR of 1.09 [95% credible interval (CI): 1.04, 1.14] for stroke deaths per 10-µg/m3 increase in PM2.5 exposure, but no significant excess for deaths from chronic respiratory disease and ischemic heart disease (IHD), all nonaccidental causes, and total mortality (after excluding stroke). Spatial adjustment attenuated the RRs for chronic respiratory disease and IHD but raised those for stroke. The RRs were consistent in various sensitivity analyses with spatial adjustment, including stratifying by levels of solid fuel exposure, by sex, and by age group, addition of climatic variables, and in supplementary case-control analyses using injury deaths as controls. DISCUSSION: Direct epidemiological measurements, despite inherent limitations, yielded associations between mortality and long-term PM2.5 inconsistent with those reported in earlier models used by the WHO to derive estimates of PM2.5 mortality in India. The modest RRs in our study are consistent with near or null mortality effects. They suggest suitable caution in estimating deaths from PM2.5 exposure based on MDS results and even more caution in extrapolating model-based associations of risk derived mostly from high-income countries to India. https://doi.org/10.1289/EHP9538.

ICMR task force project- survey of the incidence, mortality, morbidity and socio-economic burden of snakebite in India: A study protocol.

BACKGROUND: Snakebite is possibly the most neglected of the NTDs (Neglected Tropical Diseases). Half of the global deaths due to venomous snakebites, estimated at 100,000 per year, occur in India. The only representative data on snakebite available from India is the mortality data from the RGI-MDS study (Registrar General of India- 1 Million Death Study) and another study on mortality from the state of Bihar. Incidence data on snakebite is available for 2 districts of the state of West Bengal only. Hospital-based data on snakebite admissions and use of ASV are gross underestimates as most snakebite victims in rural India depend more on alternate treatment methods which do not get represented in National registries. The proposed study is a multi-centric study to determine the incidence, morbidity, mortality and economic burden of snakebites in India covering all 5 geographical zones of the country. PROTOCOL: A community level surveillance for snakebite covering 31 districts in 13 states of India in order to obtain annual incidence of snakebites from the community. Frontline health workers will be trained to gather information on new cases of snakebite over the study period of 1-year, from "wards "(smallest administrative subunit of a village or town) that they represent in the study districts. Dedicated field officers would collect data on snakebites, victim characteristics, outcomes, utilization of health facilities on a questionnaire sheet designed for this purpose. The study duration is for 18 months from April 2022 to October 2023. DISCUSSION: The study would be the first of its kind in India looking prospectively at the incidence of snakebite covering 13 states in 5 zones of India and a population of 84 million. Our study covers 6.12% of the total population of the country as compared to the incidence study conducted in Sri Lanka which covered 1% of the total population.

Moderate Rainfall and High Humidity During the Monsoon Season, Negligence in Using Malaria Protection Methods and High Proportion of Mild Symptomatic Patients Were the Driving Forces for Upsurge of Malaria Cases in 2018 Among Tea Tribe Populations in Endemic Dolonibasti Health Sub-center, Udalguri District, Assam State, North-East India.

Malaria elimination is a global priority, which India has also adopted as a target. Despite the malaria control efforts like long-lasting insecticidal nets distribution, rounds of indoor residual spray, the introduction of bi-valent rapid diagnostic tests and artemisinin combination therapy, malaria remained consistent in Dolonibasti sub-center of Orang block primary health center (BPHC) under the district Udalguri, Assam state followed by abrupt rise in cases in 2018. Therefore, we aimed to investigate the factors driving the malaria transmission in the outbreak area of Dolonibasti sub-center. Malaria epidemiological data (2008-2018) of Udalguri district and Orang BPHC was collected. The annual (2011-2018) and monthly (2013-2018) malaria and meteorological data of Dolonibasti sub-center was collected. An entomological survey, Knowledge, Attitude and Practices study among malaria cases (n = 120) from Dolonibasti was conducted. In 2018, 26.1 % (2136/ 8188) of the population of Dolonibasti were found to be malaria positive, of which 55% were adults (n = 1176). Majority of cases were from tea tribe populations (90%), either asymptomatic or with fever only, 67.5 % (81/120) had experienced malaria infection during past years. The outbreak was characterized by a strong increase in cases in June 2018, high proportion of slide falciparum rate of 26.1% (other years average, 15.8%) and high proportion of P. falciparum of 81.2 % (other years average, 84.3%). Anopheles minimus s.l. was the major vector with 28.6% positivity and high larval density in paddy fields/ drainage area. Annual relative humidity was associated with rise in malaria cases, annual parasite incidence (rs = 0.69, 90%CI; p = 0.06) and slide positivity rate (rs = 0.83, 95%CI; p = 0.01). Older people were less educated (rs = -0.66; p < 0.001), had lesser knowledge about malaria cause (rs = -0.42; χ2=21.80; p < 0.001) and prevention (rs = -0.18; p = 0.04). Malaria control practices were followed by those having knowledge about cause of malaria (rs = 0.36; χ2 = 13.50; p < 0.001) and prevention (rs = 0.40; χ2 = 17.71; p < 0.001). Altogether, 84.6% (44/52) of the respondents did not use protective measures. We described a sudden increase in malaria incidence in a rural, predominantly tea tribe population group with high illiteracy rate and ignorance on protective measures against malaria. More efforts that are concerted needed to educate the community about malaria control practices.

Non-communicable diseases as a major contributor to deaths in 12 tribal districts in India.

Background & objectives: Non-communicable diseases (NCDs) are the leading cause of death in India. Although studies have reported a high prevalence of NCD in tribal populations, there are limited data pertaining mortality due to NCDs. Therefore, in this study we estimated the proportion of deaths due to NCDs among 15 yr and older age group in tribal districts in India. Methods: We conducted a community-based survey in 12 districts (one per State) with more than 50 per cent tribal population. Data were collected using a verbal autopsy tool from the family member of the deceased. The estimated sample size was 452 deaths per district. We obtained the list of deaths for the reference period of one year and updated it during the survey. The cause of death was assigned using the International Classification of Diseases-10 classification and analyzed the proportions of causes of death. The age-standardized death rate (ASRD) was also estimated. Results: We surveyed 5292 deaths among those above 15 years of age. Overall, NCDs accounted for 66 per cent of the deaths, followed by infectious diseases (15%) and injuries (11%). Cardiovascular diseases were the leading cause of death in 10 of the 12 sites. In East Garo Hills (18%) and Lunglei (26%), neoplasms were the leading cause of death. ASRD due to NCD ranged from 426 in Kinnaur to 756 per 100,000 in East Garo Hills. Interpretation & conclusions: The findings of this community-based survey suggested that NCDs were the leading cause of death among the tribal populations in India. It is hence suggested that control of NCDs should be one of the public health priorities for tribal districts in India.

Preparedness of primary & secondary care health facilities for the management of non-communicable diseases in tribal population across 12 districts in India.

Background and objectives: Non-communicable diseases (NCDs) are highly prevalent in the tribal populations; however, there are limited data regarding health system preparedness to tackle NCDs among these populations. We estimated the availability of human resources, equipment, drugs, services and knowledge of doctors for NCD management in the selected tribal districts in India. Methods: A cross-sectional survey was conducted in 12 districts (one from each State) with at least 50 per cent tribal population in Andaman and Nicobar Islands, Himachal Pradesh, Madhya Pradesh, Odisha and eight northeastern States. Primary health centres (PHCs), community health centres (CHCs) and district/sub-district hospitals (DHs) were surveyed and data on screening and treatment services, human resources, equipment, drugs and information systems indicators were collected and analysed. The data were presented as proportions. Results: In the present study 177 facilities were surveyed, including 156 PHCs/CHCs and 21 DHs. DHs and the majority (82-96%) of the PHCs/CHCs provided outpatient treatment for diabetes and hypertension. Overall, 97 per cent of PHCs/CHCs had doctors, and 78 per cent had staff nurses. The availability of digital blood pressure monitors ranged from 35 to 43 per cent, and drugs were either not available or inadequate. Among 213 doctors, three-fourths knew the correct criteria for hypertension diagnosis, and a few correctly reported diabetes diagnosis criteria. Interpretation & conclusions: The results of this study suggest that the health system of the studied tribal districts was not adequately prepared to manage NCDs. The key challenges included inadequately trained workforce and a lack of equipment and drugs. It is suggested that capacity building and, procurement and distribution of equipment, drugs and information systems to track NCD patients should be the key focus areas of national programmes.

Impact of the COVID-19 pandemic on clean fuel programmes in India and ensuring sustainability for household energy needs.

Clean cooking energy strategies are critical for reducing air pollution, improving health, and achieving related Sustainable Development Goals. The recent COVID-19 lockdowns may impact the transition towards clean cooking fuels. The nationwide lockdown is likely to affect key factors such as energy access, income, transportation, etc., that play a role in decisions influencing household fuel use. The rural population already bears the burden of poverty and may not be able to afford and access clean cooking fuels during the lockdown. They are thus vulnerable to reversion to their traditional cooking methods using solid biomass fuels. The household air pollution caused due to the use of polluting fuels increases their susceptibility to non-communicable diseases, and thus may intensify the risk and severity of COVID-19 infection. Hence, there is an urgent need to expand sustainable energy solutions worldwide. The present study applies the DPSIR modeling framework to establish a set of comprehensive indicators for addressing the transition towards clean cooking fuels during the COVID-19 pandemic. The study also provides insights on various strategies adopted in India in response to the COVID-19 pandemic for maintaining continuity of delivering benefits under a clean cookstove program. The study offers future directions to ensure the transition towards cleaner fuels and sustainability.

White paper on venomous snakebite in India.

Venomous snakebite is one of the leading preventable causes of mortality and morbidity with tremendous socio-economic impact on the family and nation. Venomous snakebite has been relisted as a neglected tropical disease after having been removed off the list in 2013. This paper discusses the various reasons which could be attributed to the high mortality and morbidity due to venomous snakes and also provides recommendations on policy decisions, improvement on the quality of venom and anti-snake venom and in promoting awareness on how to avoid snakebite.

Incidence of leprosy in Firozabad district (Uttar Pradesh).

OBJECTIVE: To assess incidence of leprosy in Firozabad District (U.P.). MATERIALS AND METHODS: A random sample of 148,061 population was covered by this second survey, spread over 259 units (230 rural/29 urban). The survey was conducted between March 2011 and November 2012. Clinically confirmed cases detected in known disease-free population were labeled as incident cases and treated. RESULTS: The overall incidence rate of leprosy was found to be 3.4 per 10,000 person years; In healthy contacts it was 3.1, in paucibacillary contacts 29.7 while it was 89.3 in multibacillary contacts. The differences in incidence rate of these three groups were significant (P < 0.001). Incidence rate was significantly higher by age; 1.1 in persons <15 years to 8.0 in those >44 years of age, and in high endemicity areas with three or more cases. In terms of incidence rate ratio (95% confidence interval), the incidence for ages 15-24 years was 3.2 times significantly higher than for those under 15 years, 5.3 times (4.3-6.5) in ages 30-44 years and 7.0 times (5.6-8.7) for age ≥45 years. Incidence rate ratio was also significantly higher in paucibacillary contacts, by 9.5 times (7.0-13.0) and 27.7 times (18.8-40.6) in multibacillary contacts, as compared to healthy controls. Incidence rate ratio (95% confidence interval) was significantly higher by 2.9 times (2.4-3.5) in areas with endemicity status of 3 to 5 cases and by 2.0 times (1.6-2.5) in areas with >5 cases as compared to areas with no endemicity. It was 2.4 times more (1.6-3.5) in Narkhi, 2.4 times higher (1.7-3.5) in Tundla and 3.0 times higher (2.1-4.5) in Aravon blocks than in Aeka block of the district. Incidence rate was also found to be significantly higher (3.7) among females, 1.3 times higher (1.1-1.5) than in males (2.9). Incidence rate ratio (95% confidence interval) was also 2.5 times higher (1.2-5.1) among persons having reported disease of greater than 4 years in comparison to 1.5 in persons having disease for 2 to 3 years. LIMITATIONS OF STUDY: None to the best of our knowledge. CONCLUSION: The present study suggests that incidence rate of leprosy is significantly higher among persons of above 15 years, in females, among contacts of paucibacillary/multibacillary disease, in areas where >3 leprosy cases were found and in Tundla, Narkhi and Aravon blocks in Firozabad district.

Association of Nitric Oxide Synthase2 gene polymorphisms with leprosy reactions in northern Indian population.

The pathogen Mycobacterium leprae causes leprosy that affects mainly skin and nerves. Polymorphisms of certain genes are substantiated to be associated with the susceptibility/resistance to leprosy. The present investigation addressed the association of Nitric Oxide Synthase2 gene polymorphisms and leprosy in a population from northern part of India. A total of 323 leprosy cases and 288 healthy controls were genotyped for four NOS2 promoter variants (rs1800482, rs2779249, rs8078340 and rs2301369) using FRET technology in Real Time PCR. None of these SNPs in promoter sites was associated with susceptibility/resistance to leprosy. NOS2 rs1800482 was found to be monomorphic with GG genotype. However, NOS2-1026T allele was observed to be in higher frequency with leprosy cases (BL and LL) who were not suffering from any reactional episodes compared to cases with ENL reaction {OR=0.30, 95% CI (0.10-0.86), p=0.024}. NOS2-1026GT genotype was more prevalent in cases without reaction (BT, BB and BL) compared to RR reactional patients {OR=0.38, 95% CI (0.17-0.86), p=0.02}. Although haplotype analysis revealed that no haplotype was associated with leprosy susceptibility/resistance with statistical significance, GTG haplotype was noted to be more frequent in healthy controls. These SNPs are observed to be in linkage disequilibrium. Although, these SNPs are not likely to influence leprosy vulnerability, -1026G>T SNP was indicated to have noteworthy role in leprosy reactions.

WHO multidrug therapy for leprosy: epidemiology of default in treatment in Agra district, Uttar Pradesh, India.

AIM: To study the magnitude of default, time of default, its causes, and final clinical outcome. METHODS: Data collected in active surveys in Agra is analyzed. Patients were given treatment after medical confirmation and were followed up. The treatment default and other clinical outcomes were recorded. RESULTS: Patients who defaulted have comparable demographic characteristics. However, among defaulters more women (62.7% in PB, 42.6% in MB) were seen than those in treatment completers (PB 52.7% and MB 35.9%). Nerve involvement was high in treatment completers: 45.7% in PB and 91.3% in MB leprosy. Overall default rate was lower (14.8%) in ROM than (28.8%) in standard MDT for PB leprosy (χ 1 (2) = 11.6, P = 0.001) and also for MB leprosy: 9.1% in ROM compared to 34.5% in MDT (χ 1 (2) = 6.0, P = 0.015). Default rate was not different (28.8% versus 34.5%, P > 0.05) in both types of leprosy given MDT. Most patients defaulted at early stage of treatment and mainly due to manageable side effects. CONCLUSION: The default in standard MDT both for PB and MB leprosy was observed to be significantly higher than in ROM treatment. Most defaults occurred at early stage of treatment and major contribution of default is due to side effects like drowsiness, weakness, vomiting, diarrhea, and so forth, related to poor general health. Although about half of the defaulters were observed to be cured 2.2% in PB-MDT and 10.9% of MB-MDT developed disability. This is an issue due to default. Attempts are needed to increase treatment compliance. The use of specially designed disease related health education along with easily administered drug regimens may help to reduce default.

Florid reactive periostitis ossificans of long bones and digits associated with reaction in a patient with leprosy.

Florid reactive periostitis ossificans is a rare bone lesion usually occurring in the small, tubular bones of the hands and feet. This entity is a benign and aggressive periosteal reaction associated with soft tissue swelling that appears similar to a bone lesion that radiographically and clinically mimics an infectious or neoplastic process. Typically the lesions occurs in an adolescent or young adult and presents as a small area of painful swelling and erythema over the affected bone. The cause of florid reactive periostitis ossificans is not exactly known though many authors have postulated varied etiopathogenesis for the same condition. In this report, is a very rare and unusual example of this entity that has been observed in association with erythema nodosum leprosum (ENL) a type 2 lepra reaction in a Leprosy patient.